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This Study Tests Whether Taking the Medicines Empagliflozin, Linagliptin, and Metformin Together in 1 Pill is the Same as Taking Them in Separate Pills. The Study is Done in Healthy Men and Women and Measures the Amount of Each Medicine in the Blood

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03259490
Recruitment Status : Completed
First Posted : August 23, 2017
Results First Posted : February 21, 2020
Last Update Posted : March 5, 2020
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
To establish the bioequivalence of one fixed dose combination (FDC) tablet of empagliflozin/linagliptin/metformin extended release (XR) versus the free combination of empagliflozin tablet, linagliptin tablet, and metformin XR tablets administered as a single dose under fed conditions

Condition or disease Intervention/treatment Phase
Healthy Drug: Empagliflozin/linagliptin/metformin HCl Drug: Empagliflozin Drug: Linagliptin Drug: Metformin HCl Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Linagliptin/Metformin Extended Release Compared to the Free Combination of Empagliflozin, Linagliptin, and Metformin Extended Release Tablets Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Study)
Actual Study Start Date : August 31, 2017
Actual Primary Completion Date : November 13, 2017
Actual Study Completion Date : November 13, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Test Treatment
High dose empagliflozin/linagliptin/metformin XR fixed dose combination tablet
Drug: Empagliflozin/linagliptin/metformin HCl
Once daily
Other Name: TRIJARDY® XR

Experimental: Reference Treatment
Single tablets of empagliflozin + linagliptin + metformin XR
Drug: Empagliflozin
Once daily

Drug: Linagliptin
Once daily

Drug: Metformin HCl
Once daily




Primary Outcome Measures :
  1. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for Empagliflozin [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) for empagliflozin.

    Plasma concentrations and/or parameters of a subject were to be considered as non-evaluable,if for example:

    • The subject experienced emesis that occurred at or before 2 times median tmax of the respective treatment (median tmax was to be determined excluding the subjects experiencing emesis)
    • A predose concentration was >5% Cmax value of that subject
    • Missing samples/concentration data at important phases of pharmacokinetic (PK) disposition curve.

    Pharmacokinetic parameter set (PKS): This subject set included all subjects in the treated set (TS) who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was to be included in the PKS even if he/she contributed only one PK parameter value for one period to the statistical assessment.


  2. AUC0-tz for Metformin. [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    AUC0-tz for metformin.

  3. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) for Linagliptin [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for Linagliptin

  4. Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax) [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    Maximum measured concentration of the empagliflozin in plasma (Cmax)

  5. Cmax for Metformin in Plasma [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    Cmax for metformin in plasma.

  6. Cmax for Linagliptin in Plasma [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    Cmax for linagliptin in plasma.


Secondary Outcome Measures :
  1. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) for Empagliflozin (AUC(0-∞) [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin (AUC(0-∞)

  2. AUC(0-∞) for Metformin [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    AUC(0-∞) for Metformin

  3. AUC(0-∞) for Linagliptin [ Time Frame: Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose ]
    AUC(0-∞) for Linagliptin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
  • Age of 18 to 55 years (incl.)
  • BMI of 18.5 to 29.9 kg/m2 (incl.)
  • Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
  • Female subjects of childbearing potential willing to use adequate contraception.
  • Further inclusion criteria apply

Exclusion Criteria:

  • Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR), or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
  • Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (BPM)
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged as clinically relevant by the investigator
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • Further exclusion criteria apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259490


Locations
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Germany
Humanpharmakologisches Zentrum Biberach
Biberach, Germany, 88397
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Study Protocol  [PDF] June 28, 2017
Statistical Analysis Plan  [PDF] December 8, 2017

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03259490    
Other Study ID Numbers: 1361-0003
2017-000425-12 ( EudraCT Number )
First Posted: August 23, 2017    Key Record Dates
Results First Posted: February 21, 2020
Last Update Posted: March 5, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Metformin
Empagliflozin
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors